Matsumoto Kaori, Kanda Tatsuo, Wakatsuki Junichiro, Kim Young-Jin, Yokouchi Ritsuko, Sato Naho, Hasegawa Yuko, Amemiya Kenji, Hirotsu Yosuke, Hirose Sumio, Imai Yushi, Takaoka Shinya, Amano Hiroyuki, Asakawa Yukiko, Nagasaka Kouwa, Asahina Yoshiki, Kojima Yuichiro, Toyama Shodai, Mochizuki Hitoshi, Obi Shuntaro, Omata Masao
Department of Pharmacy, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan.
Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Niigata, 949-7302, Japan.
Hepatol Int. 2025 Apr 8. doi: 10.1007/s12072-025-10825-3.
Associations between the occurrence of abnormal liver function tests, an immune-related adverse event (irAE) caused by immune checkpoint inhibitors (ICIs), and treatment efficacy are unclear. We investigated the association between the incidence of these hepatic irAE occurrences and treatment response in patients treated with ICIs.
We studied 924 patients treated with ICIs to determine the relationship between the incidence of irAEs and overall survival (OS) with and without the continuation of ICIs due to hepatic irAEs.
Of 924 treated, 338 (36.6%) developed all types of irAEs. Median OS for patients with and without irAEs were 34.3 months (n = 338) and 13.1 months (n = 586), respectively (p = 2.49 × 10). Of 924, 62 (6.7%) patients developed hepatic irAE; 31 discontinued and 31 continued ICI. Of interest, median OS with and without the continuation of ICI therapy due to hepatic irAEs was 54.3 months and 11.5 months, respectively (p = 0.00589). We further compared the difference of liver function tests among the two groups. Although aminotransferases are higher among discontinued group, stigmata of impending hepatic failure were no different among these two groups.
In patients who developed hepatic irAEs, OS was longer in the continued treatment group than in the discontinued treatment group. Most patients who developed hepatic irAEs and stopped the treatment had higher aminotransferase, but often lacks the stigmata of impending hepatic failure such as prothrombin time prolongation or gradual elevation of total bilirubin. Multi-disciplinary cooperation, including hepatologists, may be important for OS improvement by the prolonged use of ICIs.
肝功能检查异常这一由免疫检查点抑制剂（ICI）引起的免疫相关不良事件（irAE）的发生与治疗疗效之间的关联尚不清楚。我们调查了这些肝脏irAE发生的发生率与接受ICI治疗患者的治疗反应之间的关联。
我们研究了924例接受ICI治疗的患者，以确定irAE的发生率与因肝脏irAE继续或不继续使用ICI情况下的总生存期（OS）之间的关系。
在924例接受治疗的患者中，338例（36.6%）出现了所有类型的irAE。有和没有irAE的患者的中位OS分别为34.3个月（n = 338）和13.1个月（n = 586）（p = 2.49×10）。在924例患者中，62例（6.7%）出现肝脏irAE；31例停用ICI，31例继续使用。有趣的是，因肝脏irAE继续或不继续ICI治疗的中位OS分别为54.3个月和11.5个月（p = 0.00589）。我们进一步比较了两组之间肝功能检查的差异。尽管停用组的转氨酶较高，但这两组之间即将发生肝衰竭的体征并无差异。
在发生肝脏irAE的患者中，继续治疗组的OS比停用治疗组更长。大多数发生肝脏irAE并停止治疗的患者转氨酶较高，但通常缺乏即将发生肝衰竭的体征，如凝血酶原时间延长或总胆红素逐渐升高。包括肝病学家在内的多学科合作对于通过延长ICI的使用来改善OS可能很重要。
